The aims of this study are to study the biliary secretion and enterohepatic circulation of three drugs that are secreted unchanged or with biologically active metabolites into the bile, diazepam, delta-9-tetrahydrocannabinol (THC) and digitoxin. The radioactively labeled drug will be administered together with a radioactively labeled bile acid to human volunteers with an indwelling nasoduodenal tube through which interval samples of duodenal bile will be collected. Concentration of drug and bile acid in interval samples of duodenal bile will be measured, and the bile acid pool size will be calculated by an isotope dilution technique. The fraction of drug removed from the bile pool in the sample will be determined from the fraction of bile acid pool removed, and the pool of drug in the bile throughout the study will thus be measured. The concentration of the drug in the plasma both free and protein-bound, will be determined from samples of blood taken with samples of duodenal bile and the kinetics of the drug in the central compartment determined. Urinary and fecal collections will also be made. With these techniques, it will be possible to calculate, at any given time, the amount of drug in the central compartment and the amount of drug sequestered, and not in equilibrium with the central compartment as well as the amount of drug in the bile pool. In further studies with human volunteers drug output will be measured using an intestinal perfusion technique: the output of drug in 24 hours will be determined and the amount of drug conserved in that period by the enterohepatic circulation calculated. Other studies will be done on bile fistula monkeys, to compare the fractional turnover rate of the drug when the enterohepatic circulation is interrupted and when it is intact, and in the presence or absence of cholecystectomy. This study will enable us to measure quantitatively the role of both the intestine and the gallbladder in the conservation of drugs. These studies will be the first in which the enterohepatic circulation of drugs will be quantitatively studied, and constitute a model for the study of any compound, exogenous or endogenous, which is secreted in the bile and may circulate enterohepatically.